The proposed studies will determine the effects of the pineal gland, in situ, as well as the effects of exogenously administered pineal compounds on the development and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in female rats subjected to the independent or combined effects of dietary restriction and light deprivation. The experiments will address the hypothesis that the antitumorigenic effects of the pineal gland are augmented in nutritionally restricted rats. The studies are also aimed at determining the effects of the pineal on prolactin (PRL) secretion at various tages of tumorigenesis after DMBA treatment, since mammary tumors are PRL dependent. Finally, the research will focus on whether the oncostatic effects of the pineal gland, in situ, and exogenously administered pineal substances are dependent or independent of alterations in PRL secretion. Several weeks following tumor induction with DMBA, rats that have been blinded or placed in long photoperiod will either be pinealectomized or left intact. A few days following surgery, the animals will either be fed ad libitum or food restricted for an additional 15 weeks. In other experiments, fed or underfed rats will receive daily injections of either melatonin or pineal fraction (UM-05R) for 15 weeks. Throughout this period, the rats will be palpated weekely for presence of tumors while the growth of individual tumors will be monitored. At 6,12 and 18 weeks after DMBA, the 24 hour levels of serum PRL will also be monitored in these animals. Through the use of PRL-stimulating or inhibiting drugs, additional experiments will determine whether the cancerostatic effects of the pineal gland, melatonin or UM-05R are dependent on alterations in PRL secretion in underfed animals. The long term objective of this research is to gain a better understanding of the complex interactions between nutrictional, photoperiodic and neuroendocrine factors inthe development and growth of PRL-dependent mammary tumors. The information derived from these studies may make possible the evaluation and eventual use of naturally occuring pineal products as potential mammary oncostatic agents, particularly in nutritionally compromised patients, in lieu of or as an adjunct to more conventional chemical and endocrine therapies.